Articular cartilage covers the end of all diarthroidal joints, allowing the bones to slide against each other without actually coming into contact with each other. Due to the lack of vascularity above the subchondral region, healing of damaged cartilage is very rare. Thus, the body generally cannot heal the articular cartilage on its own and the eventual degradation of the tissue leads to painful osteoarthritis and limited movement.
Current treatments for osteoarthritis include joint replacement, microfracturing to release mesenchymal stem cells, autograft procedures such as mosaicplasty or osteochondral autografts that require a donor site and additionally surgery, autologous chondrocyte implantation under the periosteal flap, and scaffold implantation. Unfortunately, although there are numerous treatments, none have been marked as a gold standard due to each one having its own drawbacks, especially when it comes to reproducing the exact physiological structure of articular cartilage capable of integrating with the surrounding tissue and bone.
Though the thickness of the articular cartilage covering the surface of a joint is at most 3 mm, cartilage itself has a fairly complex structure. The cartilage includes living cells (e.g., chondrocytes) and extracellular material (ECM) such as collagen, glycosaminoglycans (GAGs), and proteoglycans. The upper (superficial) zone of the cartilage layer has a higher concentration of collagen and lower concentration of GAGs attached to proteoglycans, thus providing it with the highest density of cells (e.g., chondrocytes) within the cartilage layer, as well as the highest water content. Cells are oriented in a ellipsoidal shape parallel to the subchondral surface (i.e., the surface of the underlying bone that supports the cartilage) where the collagen fibrils and proteoglycans are also arranged parallel to each other, providing strong shear resistance and lubrication. The transitional zone, which is between the superficial zone and middle (radial) zone, has a lower cell density and larger collagen nanofibers oriented in a random fashion. Lastly, the radial zone has cells that are oriented in a perpendicular fashion to the subchondral surface, and has the largest-diameter collagen fibrils with the highest concentration of proteoglycans and the lowest cell density of the three zones. The greater amount of proteoglycan and orientation of the collagen fibrils along with the cellular orientation provides compressive strength and a medium for transferring compressive load to the subchondral bone.
Damage to the cartilage layer may also involve damage to the underlying subchondral bone. Bone tissue includes progenitor cells that may be recruited to regenerate both bone and cartilage. However, critical defects are not able to be healed by the bone's natural regenerative processes. When this occurs, there is a need for a bone graft or substitute to aid in the healing. Autografts are generally considered to be the gold standard in most tissue engineering applications due to their excellent compatibility with the host, and their osteoconductivity, osteoinductivity, and osteogenicity. But the use of autografts is plagued by supply issues and donor site morbidity issues. Allografts, despite being osteoconductive and fairly abundant in supply, can be associated with disease transmissions and require processing, preservation, and sterilization steps that decrease the healing properties of the allograft. Synthetic materials, although they are usually only osteoconductive, are readily available and easy to modify in terms of structure, mechanical strength, topology, and efficacy. Further, the regenerated bone and cartilage must be integrated to prevent delamination due to the transfer of kinetic energy from the cartilage to the bone as the joint is moved.
When there is a partial depth defect (i.e., the defect does not penetrate through the cartilage layer), progenitor cells from the bone marrow cannot be recruited to form new cartilage, thus repair will be extremely limited without the bone marrow mesenchymal cells. But when there is a full thickness defect (i.e., an osteochondral defect), even though the mesenchymal stem cells are released, there is no structure on which the cells can attach, proliferate, and differentiate. In such a situation, the stem cells become fibrocartilage, which is a poor substitute for articular cartilage due to its lack of mechanical strength and lubrication properties. Thus, a bone scaffold should be included as part of the osteochondral graft for full integration of the hyaline cartilage. Through the use of osteochondral grafts, the cartilage graft can be anchored securely to the substrate below through regeneration of the bone. Synthetic osteochondral implants may also be used to promote simultaneous integration of the bone and cartilage tissue at the implant site.